Fifty-four patients meeting strict criteria for invasive pulmonary disease caused by Mycobacterium avium-intracellulare complex have been treated and followed at San Antonio State Chest Hospital during the past 15 yr. Chemotherapy with standard antituberculosis drugs was successful in effecting sputum conversion in 32 (59%) of the 54 patients. Regimens containing 2 drugs were successful in only 1 of 10 patients. If 3 or more drugs were given, 91% of those with moderately advanced cavitary disease and 64% of those with far advanced disease responded. There was no correlation between sputum conversion and use of a drug to which the organism exhibited susceptibility in vitro. No particular drug or combination of drugs was uniquely effective.